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目的:在大鼠皮层神经元研究L-吡咯烷酮羧酸(L-PGA)对谷氨酸钠(Glu)诱发神经毒性的拮抗作用。方法:原代培养的皮层神经元取自16d龄的胎鼠,与Glu作用30分钟,24小时后测定神经元的存活及培养介质中亚硝酸盐的浓度;以Fura 2-AM为细胞内[Ca~(2+)]_i荧光探针,AR-CM-MIC阳离子测定系统测定[Ca~(2+)]_i。结果:L-PGA 10-80μmol·L~(-1)浓度依赖地抑制Glu 500μmol·L~(-1)引起的神经损伤,其IC_(50)为(41±9)μmol·L~(-1),95％可信区间:(30.3-54.7)μmol·L~(-1)。L-PGA也能浓度依赖地降低Glu引起的NO释放。L-PGA 1,3,10,30,100μmol·L~(-1)对Glu 100μmol·L~(-1)引起的[Ca~(2+)]_i升高的抑制率分别为20.5％,34.4％,47.7％,70.6％,80.4％。结论:L-PGA可能通过抑制NO形成或细胞内Ca~(2+)浓度的升高而拮抗Glu的神经毒性。
AIM: To investigate the antagonistic effect of L-pyrrolidone carboxylic acid (L-PGA) on glutamate-induced neurotoxicity in rat cortical neurons. Methods: Primary cultured cortical neurons were obtained from 16-day-old fetuses and treated with Glu for 30 minutes. After 24 hours, the survival of neurons and the concentration of nitrite in the medium were measured. Fura 2-AM was used as intracellular [ Ca ~ (2 +)] _i fluorescent probe, AR-CM-MIC cation determination system [Ca ~ (2 +)] _i. Results: L-PGA 10-80μmol·L -1 inhibited neuronal damage induced by Glu 500 μmol·L -1 in a concentration-dependent manner, with IC 50 of 41 ± 9 μmol·L -1, 1), 95% confidence interval: (30.3-54.7) μmol·L -1. L-PGA also decreases Glu-induced NO release in a concentration-dependent manner. The inhibitory rates of [Ca ~ (2 +)] _ i induced by L-PGA at 1, 3, 10, 30 and 100 μmol·L -1 were 20.5% and 34.4 %, 47.7%, 70.6%, 80.4%. Conclusion: L-PGA may antagonize the neurotoxicity of Glu by inhibiting the formation of NO or increasing intracellular Ca 2+ concentration.